According to their controversial research, the crash caused the extinction of dozens of species, such as the woolly mammoth, and triggered a 1,300-year ice age that stretched around the world.
And the prehistoric hunters and gatherers in the region, known as the Clovis culture, vanished almost overnight in the aftermath.
Microscopic diamonds, so small they are barely visible in an electron microscope, are said to support their theory.
These nano-diamonds, found a few feet underground at several North American locations, including one directly on top of a Clovis site in Murray Springs, Arizona, were formed under high-temperature, high-pressure conditions created by a cosmic explosion, the researchers say.
A 'rare swarm' of comets rained fire over the entire region and melted a glacier that once covered the Great Lakes area, sending a massive flood down the Mississippi River, the researchers found.
The waves of water caused changes in the Atlantic which ushered in the ice age known as the Younger Dryas.
The comet would have hit about 65million years after the larger collision which killed off the dinosaurs.
Geophysicist Allen West, one of the paper's co-authors, said: 'Imagine these fireballs exploding in the air.
A Clovis hunter standing and looking at these things would have seen a canopy of fire as these things came in and exploded.
'There would have been no sound. There would have been massive explosions. Brilliant light, brighter than the sun.
'There would have been radiant heat. It would have been capable, at the very least, of giving him serious burns and, at the maximum, of incinerating him,' he told the Washington Post.
Douglas Kennett
Among the 35 species of mammals said to have been made extinct by the comet strike were mammoths, mastodons, sabre-toothed tigers, ground sloths, American camels, the short-faced bear, the giant beaver and the American lion.
The study was conducted by archaeologists and geologists from the universities of Oregon, California, Northern Arizona, Oklahoma and DePaul.
Their findings were published yesterday in the journal Nature.
Archaeologist Douglas Kennett, of the University of Oregon, said: 'These discoveries provide strong evidence for a cosmic impact event at approximately 12,900 years ago that would have had enormous environmental consequences for plants, animals and humans.'
However, critics believe the evidence was insufficient to blame the Earth's changes on a comet crash. They say the explosion would have left a crater of some kind.
Other sites studied included some in Oklahoma, Michigan, South Carolina, and in the Canadian province of Alberta.